Drug-drug Interaction and Acute Kidney Injury Development: A Correlation-based Network Analysis

Wenjun Zhu, Erin F. Barreto, Jingshan Li, Hyo Kyung Lee, Kianoush Kashani.

Abstract

Drug-induced nephrotoxicity is a relatively common preventable cause of acute kidney injury (AKI), providing early recognition and management. The pharmacokinetics or pharmacodynamics of drug-drug interactions may lead to additive or synergistic toxicity. The influx of new medications or off-label use of medications in the critical care setting can lead to additional nephrotoxicities, often challenging to predict or detect. This study evaluates the patterns of medication utilization, their combinations, and the related associations with AKI.

Introduction

Acute kidney injury (AKI) is a relatively common complication of acute illness. The use of potentially nephrotoxic drugs is known to induce kidney dysfunction or injury, contributing to 14–21% of cases of AKI in critically ill patients. Indeed, up to 22% of the 100 most administered drugs in adult intensive care are potentially nephrotoxic. In addition, the number of new medications, including chemotherapeutics and biological drugs with potential nephrotoxicities, continues to increase exponentially.

Materials and Methods:

Data description

The utilized data set consisted of medication administration records from patients admitted to the adult intensive care unit (ICU) of Mayo Clinic between January 2007 and May 2018. A total of 147,289 ICU admissions and 1,555 administered medication types were included in the study, which resulted in 16,603,882 medication administration instances.

Data preprocessing

The serum creatinine (SCr) and urine output (UO) criteria proposed by the Kidney Disease: Improving Global Outcomes (KDIGO) were utilized to determine the AKI incidence and stages.

Discussion

This large-scale retrospective analysis presents methods for identifying medications and drug combinations associated with AKI using correlation-based network analysis. We found 244 out of 1,096 drugs are possibly correlated with the AKI development, among which 10 of them are found to be significantly correlated when administered alone (i.e., significant isolated medications).

Citation: Zhu W, Barreto EF, Li J, Lee HK, Kashani K (2023) Drug-drug interaction and acute kidney injury development: A correlation-based network analysis. PLoS ONE 18(1): e0279928. https://doi.org/10.1371/journal.pone.0279928

Editor: Robert Jeenchen Chen, Stanford University School of Medicine, UNITED STATES

Received: May 2, 2022; Accepted: December 18, 2022; Published: January 6, 2023.

Copyright: © 2023 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: The authors report the following sources of funding: Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (Award Number: J011972), Hyo Kyung Lee was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. RS-2022-00165597), and a Korea University Grant.

Competing interests: The authors have declared that no competing interests exist.